Materials of Construction Based on Recovery Data for Cleaning Validation - Pharmaceutical Technology

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Materials of Construction Based on Recovery Data for Cleaning Validation
The material of construction is a factor in the recovery of residue in cleaning validation. An analysis of existing recovery data showed that recovery factors for drug products on various materials of construction may be categorized into several groupings.

Pharmaceutical Technology

Deviations. The RF varied more between different materials than it did between different products. The average RF by material ranged from 31.5–92.5; by product, it ranged from 47.7–102.3. The additional variability among sites was not significant relative to the variability for repeated measurements within each site. After allowing different RF means for each material and product, 97% of the remaining variability in RF was within sites, and only 3% additional variance was across sites. These results meant that across-site and within-site variability could be combined, and comparisons of materials and products across sites had essentially the same precision as comparisons made within a single site. This relationship was a very useful finding because it allows RF results to be leveraged among different sites without accounting for site-to-site differences.

The standard deviation for individual API repeated measurements of RF was 14 units. To obtain a more precise estimate of RF for a new product or material, multiple measurements of RF can be obtained at a single site. The standard error of the average of multiple measurements is less than the standard deviation. If n measurements are taken, the standard error of the mean (σmeanRF) is the standard deviation(σRF) divided by the square root of n as shown in equation 1:

To obtain an estimate of RF with a confidence interval of 10%, a recovery study can be tested at least seven times. Three repeated tests will give a confidence interval of 15%.

Table II: Material of construction grouping by recovery factor (RF).
Effect of material of construction. To identify reasonable groups of materials, the RF means were divided into groups with ranges less than or equal to the standard deviation for repeated measurements (i.e, 14 units). This split was chosen to create groups with consistent RF values within the group and different average RF means between groups. Applying this strategy resulted in five material groups (see Table II). Materials within these groups are not significantly different from each other. Of the 1262 RF values used for this analysis, 1052 (83%) are from the largest group of materials, with the second highest recovery factor ranging from 76 to 86. The other four groups of materials had only 28–115 results for each group. Since the largest group was composed of 17 of the 29 materials studied, it may be useful to consider this group as the primary reference for recovery studies.

The 1052 RF results from the largest material group were analyzed separately from the other results. Both detergents and products were included. When RF was compared across products, ignoring differences among materials within the group and ignoring sites, the standard deviation was less than 13 units. This result compared favorably to the 14-unit standard deviation for the entire data set when all products and materials were estimated separately.


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